Table 5.
Safety and efficacy data from studies on LCM in SE.
| Reference | Design | n | Patient characteristics | Study population seizure types |
LCM regimen | LCM dosing (mg) | Outcome | AEs (n of patients) |
|---|---|---|---|---|---|---|---|---|
| Kellinghaus et al. [2011] | Retrospective, descriptive, Germany |
39 | Adults mean age: 63 (18–90) years Male: 18 patients (46%) Female: 21 patients (54%) |
Convulsive generalized 6/39 (15%) Complex partial 17/39 (44%) Simple focal 16/39 (41%) |
LCM 1st/2nd: 5/39 (13%) LCM 3rd: 19/39 (49%) LCM 4th or later: 15/39 (38%) latency to LCM onset (total, hour): mean: 116.5 (0.5–1440) |
Bolus: 328 mg (200–400) 1st day: 424 mg (200–600) |
Overall termination after LCM, no further AED: 44% <6 h after LCM IV, no other AED after LCM: 7/39, 18% >6 h after LCM IV no other AED after LCM 10/39, 26% success rate LCM first/second: 3/5 (60%) success rate LCM third 11/19 (58%) success rate LCM fourth or later 3/15 (20%) |
Overall: 30 (77%) allergic skin reaction (1) (possible domperidone effect) sedation (25) (always after administration of benzodiazepines, barbiturates or propofol) Hypotension (4) (association with propofol or phenytoin) no ECG changes observed |
| Albers et al. [2011] | Retrospective, descriptive, Germany |
7 | Adults 33–83 years Male: 6 patients (86%) Female: 1 patient (14%) |
Focal SE (7/7) | LCM median 4th AED (range 2–5) | Initial dose: 400 mg IV Maintenance: 400 mg/day IV |
Response to LCM within 24 h: 100% | No side effects or interactions attributable to LCM |
| Goodwin et al. [2011] | Retrospective, descriptive, USA |
9 | Adults mean age: 63 (47–89) years Male: 2 patients (22%) Female: 7 patients (78%) |
NCSE 6/9 (67%) CSE 3/9 (33%) |
LCM median 3rd AED (range 2–5) | Initial dose: 200 mg IV Maintenance: 400 mg/day Follow up: 48 h prior to RSE onset to 7 days after initiation of LCM |
No response to LCM (0/9), defined as absence of EEG seizure activity within 4 h or for 24 h following emergence from burst suppression | Overall: 2 (22%) Acute angioedema: 2 (22%) |
| Hofler et al. [2011] | Retrospective, descriptive, Austria |
31 | Adults median age: 62 (22–95) years Male: 17 patients (55%) Female: 14 patients (45%) |
CSE 11/31 (36%) FSE 10/31 (32%) NCSE 10/31 (32%) |
LCM 1st 7% (2/31); LCM 2nd 19% (6/31); LCM 3rd 48% (15/31); LCM 4th or later 26% (8/31) |
Initial dose: median 200 (200–400) mg IV Maintenance: median 200 (0–400) mg/day IV Follow up: 24 h after IV LCM |
Termination: SE overall: 25 (81%) CSE: 10/11 (91%) FSE: 8/10 (80%) NCSE: 7/10 (70%) |
Not reported |
| Koubeissi et al. [2011] | Retrospective, descriptive, USA |
4 | Adults mean age: 66 (53–79) years Female: 4 Male: 0 |
NCSE | LCM median 4th AED (range 2–5) | Initial: 50–100 mg IV maintenance dose: 100–200 mg twice a day Interval from NCSE onset to LCM therapy: 3–50 h |
Seizure cessation: 100% Time from begin of LCM therapy to seizure control: 15 min to 2 h |
No AEs attributed to IV LCM, including allergic reactions, cardiac, or respiratory problems (0%) |
| Rantsch et al. [2011] | Retrospective, descriptive, Germany |
9 (10 episodes) |
Adults mean age: 67 (52–84) years Male: 3 patients Female: 6 patients |
NCSE: 80% EPC: 20% |
Median LCM as 6th drug (range 4–12) | Loading dose: 50–100 mg IV as a bolus or 50 mg IV twice a day |
Seizure cessation in 2 of 10 episodes: 20% | No AEs detected. (0%) |
| Cherry et al. [2012] | Retrospective, descriptive, USA |
24 patients with SE and isolated seizures (10 patients with SE: 13 episodes) |
Adults SE group: Mean age: 51 (24–80) years Male: 5 patients Female: 8 patients |
SE group: NCSE 7/13 (54%) Focal motor with altered consciousness 4/13 (31%) Myoclonic 0 Generalized convulsive 2/13 (15%) |
LCM median 3rd AED (range 1–7) | SE group: loading/initial dose: mean (range) 180.8 mg (100–400) Infusion rate: mean (range) 3.33 mg/min (1.67–6.67) maintenance dose: mean (range) 361.5 mg/day (300–400) Time from seizure onset to LCM initiation: mean (hour) 39.5 (6.5–74) |
SE group: seizure cessation 5/13 (38%) mean time to outcome (hour) 11.2 (1.5–21) >50% Reduction in seizures 7/13 (54%) mean time to outcome (hour) 8 (2–17) |
Overall: 4/13 (31%) Hypotension (decreased systolic BP > 20 mm compared with baseline in absence of other BP lowering drugs) 3/13 (23%) Hypersensitivity reaction (rash and angioedema): 0 Cardiac arrhythmia: 0 Creatinine > 2.0: 0 Elevated liver function tests (>2x baseline) 1 (4%) |
| Mnatsakanyan et al. [2012] | Retrospective, descriptive, USA |
10 | Age: 16–90 years Male: 4 patients (40%) Female: 6 patients (60%) |
NCSE | Median as 4th AED (range 2–8) | Initial dose: median 200– 300 mg IV within 30 min Maintenance dose: 200–400 mg/day follow up: 1 week – 10 months |
SE termination: 7 (70%) | Overall: 0 |
| Jain and Harvey [2012] | Retrospective, descriptive | 3 | Children range 12–17 years |
refractory tonic SE | LCM as 4th or later AED duration of SE prior to LCM: 8–29 h |
LCM bolus doses (2–2.5 mg/kg; 50–200 mg in the 1st 2 h) |
SE termination 3/3 (1 after second dose) | Oculogyric crisis on day 4 (1) chorea on day 5 (1) |
| Miro et al. [2013] | Prospective, descriptive, Spain |
34 | Adults Mean age: 60 (22–86) years Male: 18 patients (53%) Female: 16 patients (47%) |
FMSE 28/34 (82%) NCSE 5/34 (15%) GCSE 1/34 (3%) |
Median interval latency: 48 (1–250) h after SE therapy initiation | Initial dose: 100–400 mg IV bolus (I) 100 mg IV: 1 (3%) (II) 200 mg IV: 7 (21%) (III) 300 mg IV 9 (26%) (IV) 400 mg IV 17 (50%) Maintenance: mean 324 (100–600) mg orally or IV/day |
SE termination = LCM efficacy overall: 22/34 (64.7%) LCM 3rd/4th 13/34 (72.2%) LCM 5th or later 9/34 (56.3%) |
Overall: 2 (6%) Diplopia: 1 Confusion/nystagmus: 1 |
| Sutter et al. [2013] | Retrospective, comparative cohort, Switzerland | 111 (86 included in analysis) | LCM group: mean age: 65 ± 15 years Male: 20 patients (44%) Female: 25 patients (56%) non-LCM group: Mean age: 60 ± 17 years Male: 25 patients (61%) Female: 16 patients (39%) |
LCM group: focal or absence SE 17 patients (38%) NCSE 27 (60%) GCSE 1 (2%) Non-LCM group: focal or absence SE 12 patients (29%) NCSE 25 (61%) GCSE 4 (10%) |
Order in which IV LCM was administered: Started simultaneously with 2nd AED: 3 (7%) 3rd AED 22 (49%) 4th AED 14 (31%) 5th AED 3 (7%) 6th AED 3 (7%) LCM as an adjunctive AED on mean as 4th drug (range 2–6) |
200 mg IV Renal dysfunction: dose reduction Obesity (n = 1): 600 mg IV |
Duration of SE (mean ± SD): LCM: 87 ± 159, Non-LCM: 134 ± 189, Seizure control: LCM: 93%, Non-LCM: 85% Multivariable analysis (adjustment for age): Duration of SE (hour): OR: −35.9 95% CI: −111.2–39.4, p = 0.346 Seizure control OR: 2.40 95% CI: 0.6–10.5, p = 0.246 Death OR: 0.34 95% CI: 0.1–0.9, p = 0.035 |
Overall: 0 |
| Belcastro et al. [2013] | Prospective, descriptive, Italy |
16 | Adults 77 ± 7 years of age Male: 7 patients Female: 9 patients |
Stroke Patients, NCSE (7 simple, 9 complex) | LCM as initial drug | IV LCM as initial treatment, loading dose of 400 mg over 30 min, mean maintenance dose of 400 mg per day |
Seizure control 7/16 (44%) | No significant AEs |
| Santamarina et al. [2013] | Retrospective, descriptive | 92 LCM group: n = 31 non-LCM group: n = 61 |
Adults LCM group: mean age 62 (21–85) years, Male: 17 patients (55%) Female: 14 patients (45%) Non- LCM group: mean age 63 (20–91) years, Male: 32 patients (42%) Female: 29 patients (48%) |
LCM group: Generalized convulsive 4/31 (12.9 %) Nonconvulsive 10/31 (32.3 %) Motor focal or epilepsia partialis continua 17/31 (54.8 %) Non-LCM group: Generalized convulsive 15/61 (24.6 %) Nonconvulsive 13/61 (21 %) Motor focal or epilepsia partialis continua 33/61 (54.1 %) |
LCM as 2nd/ 3rd option (n = 13) LCM as 4th/ 5th option (n = 18) |
LCM as 2nd/ 3rd option Infusion rate (mg/ min, median) 26.7 (23–40) Maintenance dose (mg/day) 400 LCM as 4th/ 5th option Infusion rate (mg/ min, median) 31.7 (25–40) Maintenance dose (mg/day) 400 |
Duration of SE prior to LCM (hour, median) 30 (3–200) Time to response to LCM (hour, median) 20 (1–96) LCM as 2nd/ 3rd option Responder rate 11 (84.6 %) Time to response to LCM (hour) 10 (1–72) LCM as 4th/ 5th option Responder 10 (55.6 %) Time to response to LCM (hour) 48 (20–96) |
Dizziness (2) PR interval prolongation without clear clinical symptoms (2) |
| Legros et al. [2014] | Prospective, descriptive, Belgium |
25 200 mg: n = 11 400 mg: n = 14 |
Adults 200 mg: Median age 54 (36–74) years Male: 7 patients (64%) Female: 4 patients (36%) 400 mg: Median age 60 (17–84) years Male: 6 patients (43%) Female: 8 patients (57%) |
RSE (84%) SC (16%) Convulsive/nonconvulsive/generalized/partial |
Mean number of AEDs failed before LCM: 3 (range 2–5 200 mg group, 1–5 400 mg group) | Initial dose: (I) 200 mg IV over 15 min. (II) 400 mg IV over 15 min. Maintenance: 400 mg/day orally Follow up: after administration, 3 h and 24 h |
Response to LCM Overall: 9 (36%) 200 mg: 2 (18%) 400 mg: 7 (50%) (p = 0.2) Early response (⩽ 3 h) to LCM 200 mg: 0 (0%) 400 mg: 4 (29%) (p = 0.023) |
Overall: 5 (20%) Myoclonus/confusion: 1 Increased seizure severity: 1 Dizziness: 1 Ataxia: 1 Increased liver enzyme: 1 |
| Kellinghaus et al. [2014] | Retrospective, comparative cohort, Germany |
46 | Adults Median age: 68 (18–90) years Male: 23 patients (50%) Female: 23 patients (50%) |
Focal SE: 19/46 (41%) NCSE: 15/46 (34%) GCSE: 12/46 (26%) |
3rd AED overall: 46 3rd AED = LCM: 21 3rd AED = PHT: 15 |
Median interval latency from SE onset to therapy: 0.75 (0.2 –336) hour median 3rd AED dose: LCM: 400 (200–800) mg IV versus PHT: 1500 (750 – 1500) mg |
SE termination after 3rd AED treatment: LCM 7/21 (33%) PHT 6/15 (40%) (p = 0.68) Median time to seizure termination: LCM 9.5 (0.5–240) h PHT 13.5 (0.5–28.5) h (p = 0.48) |
Overall: LCM: 0/21 PHT: 4/15 |
| Garces et al. [2014] | Retrospective, descriptive | 55 | Adults Mean age: 65.1 (18–90) years Male: 21 patients (38%) Female: 34 patients (62%) |
NCSE 43 (78.2%) GCSE 5 (9.1%) FMSE 7 (12.7%) | Order of IV LCM 1st: 1.8% 2nd: 40% 3rd: 34.5% 4th or greater: 23.6% |
50–400 mg IV (median 200 mg) Subsequent dose 50– 400 mg IV /day (median 200 mg/day) |
SE cessation after administration: 70.9% (39/55) SE cessation<24 h after administration: 49.1% (27/55) Time to seizure cessation: 18 h (mean) |
Overall: 8/55 (14.5%) Somnolence (5) Nausea (2) Dizziness (1) Diplopia (1) PR interval prolongation (1) AV block (1) Discontinuation: 2/55 (3.6%) |
| Grosso et al. [2014c] | Retrospective, descriptive, Italy |
11 | Children Mean age: 9.4 (3–16) years Male: 5 patients Female: 6 patients |
Refractory SE: convulsive 6/11 (54%) non-convulsive 5/11 (46%) |
LCM as fourth or later drug LCM was started after a mean latency interval of 58 h (range 22–576 h) |
mean initial bolus dose of LCM: 8.6 mg/kg | SE cessation overall: 5/11 (45%) | No AEs |
| Poddar et al. [2016] | Retrospective, descriptive | 9 | Children mean age: 5.7 years (3 months to 16 years) Male: 4 patients Female: 5 patients |
generalized: 1 complex partial: 6 (1 with secondary generalization) complex partial, myoclonic, generalized tonic 1 epilepsia partialis continua 1 |
range: 2–6 | mean initial or loading dose: 8.7 mg/kg (3.3– 10 mg/kg) average total amount of IV LCM administered within the initial 24 h: 13.8 mg/kg (4.3–15 mg/kg). |
efficacious in 7/9 (77.8%) patients 4/9 patients (44.4%) seizure-free |
Bradycardia (1) |
AE, adverse effect; AED, anti epileptic drug; AV, atrioventricular; BP, blood pressure; CI, confidence interval; CSE, convulsive status epilepticus; ECG, electrocardiogram; EEG, electroencephalogram; FMSE, focal motor status epilepticus; GCSE, generalized, convulsive status epilepticus; IV, intravenous; LCM, lacosamide; NCSE, nonconvulsive status epilepticus; OR, odds ratio; PHT, phenytoin; RSE, refractory status epilepticus; SD, standard deviation; SE, status epilepticus